Low grade papillary superficial bladder tumors are the most common form of transitional cell carcinoma and current trends indicate that their prevalence is increasing. Although rarely progressing toward infiltration and metastasis, these tumors have a high recurrence rate and their detection by urine cytology is difficult because of the normal light microscopic appearance of the cells and their normal DNA content. This tumor type appears fairly distinct from the most aggressive carcinomas, although some overlapping and continuity clearly exists. It has been suggested that they represent two separate diseases.
Serological characterization of bladder cancer phenotypes with monoclonal antibodies has revealed a high degree of antigenic diversity. Most antigens are markers of the normal urothelial differentiation lineage or are acquired at a late stage of tumor progression. Studies have failed, however, to identify specific antigens of well-differentiated tumors, possibly due to the close resemblance of these cells to their normal counterpart.
The analysis of human bladder cancers with monoclonal antibodies has progressed rapidly in recent years, and several determinants on proteins or glycolipids have been recognized. In most previous studies, antibodies were obtained after immunization and screening on cultured cells and all antibodies described were reactive with human cancer lines.
In the few studies where antigen phenotype was correlated with tumor histologic grade and stage, the expression of antigens with apparent tumor specificity, not expressed on normal urothelium, was limited to the most advanced cancers. Om5 antigen was found to be the most restricted antigen with specificity for tumors of urothelial origin, particularly the superficial tumors. However this antigen, defined by monoclonal antibodies obtained from immunization with extracts of well-differentiated bladder tumor cells, was also expressed on normal urothelium of 55% of individuals tested.
Identification of unique antigens of human tumor cells in adult tissues has remained difficult despite the advent of hybridoma technology. One may question the existence of such antigens, or else the limits of the mouse immune repertoire. However an alternative explanation may be found in antigenic competition, which has long been recognized as one of the reasons for limited antibody production against antigen mixtures. This phenomenon may be particularly important when attempting to raise specific antibodies against tumor cells that retain much of the differentiated phenotype of their tissue of origin, so that tumor-specific antigens represent a very small minority of the total antigens.
Therefore the production of a monoclonal antibody defining an antigen restricted to superficial bladder tumors and non-reactive with normal urothelial cells would be highly desirable.